The present invention relates generally to a method for treating endometrial hyperplasia or uterine cancer in menopausal women, and more particularly to such a method that involves performing endometrial ablation in combination with unopposed estrogen hormone therapy.
Female patients are often faced with conditions that may make them susceptible to endometrial hyperplasia or cancer. Included in these conditions are genetics, hormonal and chemotherapies such as Tamoxifen for breast cancer, and hormone replacement therapies such as estrogen or estrogen-progestin therapy. Hormone replacement therapies are often recommended for female patients that are perimenopausal. Perimenopausal patients are defined as premenopausal patients that are in transition to becoming menopausal. These patients exhibit the typical symptoms of the transition to menopause. Perimenopause is the last stage of premenopause. Premenopausal is defined as those patients that have not reached menopause. Menopausal and postmenopausal are synonymous terms. Patients that have reached menopause no longer have menstrual cycles. The benefit of hormone replacement therapy is that it mitigates many of the undesirable symptoms associated with the perimenopausal period. These symptoms includexe2x80x94hot flashes, vaginal dryness, dyspareunia, increased urinary frequency, and mood swings. Hormone replacement therapies are also recommended for menopausal female patients to address disorders of aging. These can include osteoporosis, coronary artery disease and potentially Alzheimer disease and colon cancer.
Estrogen provides the primary benefit in hormone therapy. However, it has been associated with endometrial hyperplasia and sometimes cancer. To minimize these undesirable side-effects, progestin is often administered along with estrogen. While progestin does help to minimize the undesirable effects of estrogen it has its own risks and side effects. Progestin also tends to antagonize and reduce the desired beneficial effects of estrogen. Often, patients will refuse treatment or take themselves off treatment because of the deleterious aspects of progestin. Risks include reduction of estrogen benefit on heart (i.e., reduces estrogen benefit in addressing coronary artery disease) by altering lipid profile. Progestin also causes irregular menstrual bleeding. There is also evidence that progestin increases the risk of breast cancer. Other side effects include bloating, breast tenderness, fluid retention and mood swings. In many regards progestin antagonizes the benefits of estrogen.
To summarize, estrogen treats menopausal symptoms and reduces risk of heart disease, osteoporosis and possibly Alzheimer""s Disease and colon cancer, but unopposed estrogen is believed to be associated with increased risk of endometrial hyperplasia and sometimes cancer. Progestin is prescribed to prevent these potential problems. Progestin, however, antagonizes the benefit of estrogen on CVD and causes unpleasant side-effects which constitutes a major reason for discontinuance of hormone replacement therapy.
More recently, there have been drugs developed that may prove to be effective in addressing osteoporosis. However, these drugs do little to address the many other needs of female patients.
Hysterectomy is also a method of preventing endometrial hyperplasia and uterine cancer. This is a highly invasive procedure that also has numerous disadvantages.
Endometrial ablation and resection is a current therapy for perimenopausal female patients for the purpose of minimizing excessive uterine bleeding (Aletebi F A; Vilos G A; Eskandar M A, Journal of the American Association of Gynecologic Laparoscopists November 1999, 6 (4) p435-9; Franchini et al. Gynaecological Endoscopy 1999, 8/2 p111-114). However, it has never been applied to these patients for the purpose of minimizing, reducing or eliminating endometrial hyperplasia and/or uterine cancer.
For the purposes of this disclosure, endometrial ablation is defined as the destruction and removal of endometrial tissue. This may be achieved by the use of laser, thermal, cryotheraputic, ultrasound, radio frequency, electrical, electromagnetic, microwave, roller ball electrodes, loop electrodes, chemical, photochemical, mechanical or any other suitable means.
Postmenopausal women with abnormal uterine bleeding (AUB) and hyperplasia without atypia have been treated with transcervical hysteroscopic endometrial resection (Cianferoni et al., Journal of the American Association of Gynecologic Laparoscopists May 1999, 6 (2) p151-4). This was shown to be an effective treatment in achieving regression of endometrial hyperplasia and preventing its recurrence.
Endometrial ablation and resection therapy has also been applied to female patients in perimenopause and postmenopause that experience excessive uterine bleeding in order to address bleeding disorders that could not be treated by modification of steroid dosages during sequential hormone replacement therapy (Romer, Gynecologic and Obstetric Investigation, 1999, 47 (4), p255-7). In these patients there was no intrauterine cause for the bleeding. Following endometrial ablation, patients received a combined hormone replacement therapy and remained amenorrheic.
One study has been performed in postmenopausal women to determine whether women who have undergone transcervical resection of the endometrium could subsequently receive hormone therapy consisting of unopposed estrogen. Istre et al. (Obstetrics and Gynecology November 1996, 88 (5) p767-70). Istre et al. reported the use of a particular type of endometrial ablation, transcervical resection of the endometrium, of sixty-two postmenopausal women. Both groups were administered continuous hormone replacement therapies. One therapy was 17-beta-estradiol 2 mg alone and the other was 17-beta-estradiol 2 mg combined with norethisterone 1 mg. However, this study concluded that postmenopausal hormone replacement therapy in patients who have undergone transcervical resection of the endometrium should include progestin for protection of the endometrium. Aspects of this study teach away from the approach proposed by this invention.
While perimenopausal and postmenopausal women have been treated with various forms of endometrial ablation (generally for treatment of unwanted bleeding), it has never been a therapy used specifically to prevent endometrial hyperplasia and/or uterine cancer. Further, it has never been discovered that certain endometrial ablation techniques can be used in combination with unopposed estrogen hormone therapy to prevent enodmetrial hyperplasia and/or uterine cancer.
Therefore, there is a need for a better method of treatment for female patients that are susceptible to developing endometrial hyperplasia and/or endometrial cancer. There is also a need for a way to minimize or eliminate the amount of progestin that is required to reduce unwanted side effects of estrogen, and also allow for the retention of the uterus.
One object of this invention relates to a method and apparatus of treatment for female patients having a uterus. In particular, the invention relates to a treatment that reduces, minimizes or eliminates the onset of endometrial hyperplasia and/or uterine cancer. The treatment is affected by the alteration of at least a part of the endometrial lining of the uterus. Most particularly, the invention relates to ablation of the endometrial lining by techniques that ablate substantially all of the endometrial lining, followed by unopposed estrogen therapy.
In particular, a method is provided for treating endometrial hyperplasia or uterine cancer in menopausal women including performing endometrial ablation in a menopausal woman to thereby ablate substantially all of the endometrium, and administering a hormone therapy comprising unopposed estrogen. According to one embodiment, the performing step is performed using a thermal ablation technique. According to another embodiment, the performing step is performed using a heated fluid in the uterine cavity. According to yet another embodiment, the performing step is performed using a heated fluid within a distendable bladder that substantially conforms to an interior shape of the uterus.
In yet another embodiment, a method is provided for treating endometrial hyperplasia or uterine cancer in menopausal women including performing endometrial ablation using a thermal ablation technique, and administering a hormone therapy comprising unopposed estrogen. In another embodiment, the thermal ablation technique is a heated balloon thermal ablation technique.
These and other features and advantages of the present invention will become apparent from the following more detailed description, when taken in conjunction with the accompanying drawings which illustrate, by way of example, the principles of the invention.